0000000000042579
AUTHOR
Ulrich Jahnel
Differential electrophysiologic and inotropic effects of phenylephrine in atrial and ventricular heart muscle preparations from rats.
Stimulation of alpha 1-adrenoceptors evokes a different pattern of inotropic responses in atrial and ventricular heart muscle preparations from rats. The inotropic effects are accompanied by different changes in membrane potential. In an attempt to clarify the question whether or to which extent these events are causally related, the effects of phenylephrine on force of contraction, transmembrane potential, Ca2+ current (ICa) and K+ currents were comparatively studied in either tissue. In atrial preparations, phenylephrine 10 mumol/l caused an increase in force of contraction, a marked prolongation of the action potential duration and a depolarization of the membrane at rest. In the ventric…
L-type calcium channel activity in human atrial myocytes as influenced by 5-HT.
5-Hydroxytryptamine (10 mumol/l; 5-HT) exerted a positive inotropic effect associated with an increase in the Ca2+ current (ICa) in the human right atrium. For detailed analysis, L-type Ca2+ channel currents were recorded from cell-attached patches using 100 mmol/l Ba2+ as charge carrier. Ca2+ channel activity was identified, first, by burst-like inwardly directed currents and, second, by the appearance of long channel openings promoted by Bay K 8644 (1 mumol/l) upon repetitive depolarizations from -80 to 0 mV. The unitary conductance of the Ca2+ channel amounted to 25.8 pS. During superfusion with 5-HT, ensemble averaged (mean) current was enhanced by about 60%. The increase in mean curren…
Electrophysiologic and inotropic effects of alpha-adrenoceptor stimulation in human isolated atrial heart muscle.
The effects of α-adrenoceptor stimulation on force of contraction were investigated in human atrial heart muscle and compared with those of β-adrenoceptor stimulation. The maximal positive inotropic effect produced by stimulation of α-adrenoceptors with phenylephrine (in the presence of atenolol 10 μmol/l) was significantly smaller than that seen in response to β-adrenoceptor stimulation with isoprenaline. The maximal effect of phenylephrine (25% of the maximal effect of isoprenaline) required far higher concentrations (1 mmol/l) than isoprenaline (100 nmol/l); the EC50 values amounted to 33.1 μmol/l and 3.3 nmol/l, respectively. In the presence of the α-adrenoceptor blocking agent phentola…
Characterization of adenosine receptors in guinea-pig isolated left atria
1. The effects of purinergic stimulation on action potential, force of contraction, 86Rb efflux and 45Ca uptake were investigated in guinea-pig left atria. 2. Adenosine exerted a negative inotropic effect which was antagonized by adenosine deaminase but enhanced by dipyridamole. 3. The negative inotropic effect of adenosine was mimicked by 5'-(N-ethyl)-carboxamido-adenosine (NECA) and the isomers of N6-(phenyl-isopropyl)-adenosine, R-PIA and S-PIA. NECA and R-PIA were about 100 times more potent than adenosine, whereas R-PIA was about 100 times more potent than S-PIA. 4. The inotropic effects of adenosine (in the presence of dipyridamole), NECA, R-PIA and S-PIA were competitively antagonize…
On the mechanism of action of phenylephrine in rat atrial heart muscle
Both in rat left atrial heart and in aortic smooth muscle preparations, phenylephrine (PE) caused a concentration-dependent increase in force of contraction (FC) in the presence of atenolol (10 mumol/l), which was antagonized by phentolamine, prazosin and WB 4101 in a competitive manner. The pA2 values of the antagonists in the cardiac tissue were 10-20fold lower than those in the rat thoracic aorta. In the spontaneously beating right atrium, PE exerted a positive chronotropic action, which was not significantly antagonized by phentolamine or prazosin. It is therefore assumed that the effects of phenylephrine in the left atrium and in the aorta are mediated by different subtypes of alpha 1-…
Different mechanisms of the inhibition of the transient outward current in rat ventricular myocytes.
The mechanism of drug-induced inhibition of the transient outward current, Ito, has been investigated in rat ventricular myocytes using the whole cell patch clamp technique. Ito was activated by 300 ms depolarizing voltage clamp steps in 10 mV increments from −50 mV up to +40 mV. At +40 mV, Ito peaked after about 3 ms, and the time course of inactivation was appropriately described by two time constants, τfast = 17 ms and τslow = 203 ms. Verapamil, quinidine sulfate and nifedipine preferentially depressed Ito at the end of the 300 ms depolarizing voltage clamp step; the inactivation of Ito was accelerated by all drugs, whereas peak Ito was less affected. The time course of drug action at +4…
Modulation of cytosolic free calcium concentration by ?1-adrenoceptors in rat atrial cells
The effects of α1-adrenoceptor stimulation by phenylephrine (PE) and β-adrenoceptor stimulation by isoprenaline (ISO) on Ca2+ current (ICa) and free intracellular Ca2+ concentration ([Ca2+]i) were studied in isolated atrial myocytes from rat hearts. PE did not significantly affect the magnitude of ICa, whereas large increases of peak ICa were observed in response to ISO. In electrically driven cells, PE evoked a concentration-dependent, gradual increase in diastolic [Ca2+]i and, initially, an increase in the height of peak [Ca2+]i transients. When the diastolic [Ca2+]i was increased to a greater extent, the amplitude of [Ca2+]i transients was decreased. Simultaneous measurements of [Ca2+]i …
Depolarization-induced influx of sodium in response to phenylephrine in rat atrial heart muscle.
1. The effects of alpha 1-adrenoceptor stimulation on transmembrane potential, currents and ion fluxes were investigated in multicellular preparations and/or single cells obtained from the left atrium of rat hearts. 2. In multicellular preparations, phenylephrine caused a concentration-dependent positive inotropic effect, an increase in action potential duration, and a decrease in resting potential; the effects were antagonized by phentolamine. 3. In the presence of phenylephrine (100 mumol/1), two levels of resting potential were observed when the preparations were, alternately, electrically stimulated or kept at rest (-74 +/- 1 mV during activity and -62 +/- 4 mV at rest; mean +/- S.E.M.;…
Adrenoceptor-mediated effects on calcium channel currents are antagonized by 5?-(N-ethyl)-carboxamido-adenosine in guinea-pig atrial cells
In guinea-pig atrial myocytes, the effects of the adenosine analogue 5′-(N-ethyl)-carboxamido-adenosine (NECA) in the presence of isoprenaline (ISO) on Ca2+ channel activity were analyzed. Single Ca2+ channel currents were recorded from cell-attached patches by application of several hundred 100 ms depolarizing steps. Under control conditions, burstlike activity of channel openings during some depolarizing steps were followed by variably long periods of quiescence (blank sweeps). During superfusion with ISO (100 nmol/l), ensemble-averaged (mean) current was increased by about 150%. The underlying mechanism was found to be a significant increase in the channel availability, defined as the ra…
Contribution of both ?- and ?-adrenoceptors to the inotropic effects of catecholamines in the rabbit heart
The functional role of alpha-adrenoceptors was investigated in different parts of the rabbit heart. Phenylephrine (PE) caused a marked increase in force of contraction (Fc) and a prolongation of the action potential (AP) in preparations from the left atrium and the right ventricle. The response was less pronounced in the right atrium and in the left ventricle, whereas APs of spontaneously beating sinoatrial preparations remained completely unchanged. Phentolamine as well as the diesters phorbol 12,13 dibutyrate (PDBu) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA) eliminated the effects of PE. The contribution of alpha-adrenoceptors to the effects of adrenaline (Adr) and noradrenaline (NA) …
Positive inotropic response to 5-HT in human atrial but not in ventricular heart muscle
The effects of 5-hydroxytryptamine (5-HT) on force of contraction (FC), action potential (AP) and calcium current (ICa) were studied in human right atrial and left ventricular heart muscle. 5-HT exerted a concentration-dependent increase in FC in multicellular atrial preparations; the EC50 was approximately 3 x 10(-7) mol/l. Maximal increases in FC (252 +/- 58% of control values; mean +/- SEM, n = 6) were obtained at 5-HT 10(-5) mol/l. At this concentration, ICa was increased four- to sevenfold in enzymatically isolated atrial myocytes. In contrast, ventricular preparations did not respond to 5-HT; FC, AP and ICa remained unaffected. In the same preparations, FC was increased by isoprenalin…